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      Role of the Medial Orbitofrontal Cortex and Ventral Tegmental Area in Effort-Related Responding

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          Abstract

          The posterior subdivision of the medial orbitofrontal cortex (mOFC-p) mediates the willingness to expend effort to reach a selected goal. However, the neural circuitry through which the mOFC-p modulates effort-related function is as yet unknown. The mOFC-p projects prominently to the posterior ventral tegmental area (pVTA). Therefore, we analyzed the role of the mOFC-p and interactions with the pVTA in effort-related responding using a combination of behavioral, pharmacological, and neural circuit analysis methods in rats. Pharmacological inhibition of the mOFC-p was found to increase lever pressing for food under a progressive ratio (PR) schedule of reinforcement. These findings provide further support for a modulation of effort-related function by the mOFC-p. Then, we investigated effects of disconnecting the mOFC-p and pVTA on PR responding using unilateral pharmacological inhibition of both areas. This asymmetric intervention was also found to increase PR responding suggesting that the mOFC-p controls effort-related function through interactions with the pVTA. Possibly, a reduced excitatory mOFC-p drive on pVTA gamma-aminobutyric acid (GABA)ergic relays disinhibits VTA dopamine neurons which are known to support PR responding. Collectively, our findings suggest that the mOFC-p and pVTA are key components of a neural circuit mediating the willingness to expend effort to reach a goal.

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          Most cited references38

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          Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.

          Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral shell and lateral tubercle). These findings complement the recent behavioral findings that cocaine and amphetamine are more rewarding when administered into the ventromedial striatum than into the ventrolateral striatum. Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA. A review of the literature suggests that (1) the midbrain has corresponding zones for the accumbens core and medial shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens shell; and (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function. The medial projection system is important in the regulation of arousal characterized by affect and drive and plays a different role in goal-directed learning than the lateral projection system, as described in the variation-selection hypothesis of striatal functional organization.
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            Ventral tegmental area: cellular heterogeneity, connectivity and behaviour

            Dopamine-releasing neurons of the ventral tegmental area (VTA) have central roles in reward-related and goal-directed behaviours. VTA dopamine-releasing neurons are heterogeneous in their afferent and efferent connectivity and, in some cases, release GABA or glutamate in addition to dopamine. Recent findings show that motivational signals
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              Orbitofrontal cortex as a cognitive map of task space.

              Orbitofrontal cortex (OFC) has long been known to play an important role in decision making. However, the exact nature of that role has remained elusive. Here, we propose a unifying theory of OFC function. We hypothesize that OFC provides an abstraction of currently available information in the form of a labeling of the current task state, which is used for reinforcement learning (RL) elsewhere in the brain. This function is especially critical when task states include unobservable information, for instance, from working memory. We use this framework to explain classic findings in reversal learning, delayed alternation, extinction, and devaluation as well as more recent findings showing the effect of OFC lesions on the firing of dopaminergic neurons in ventral tegmental area (VTA) in rodents performing an RL task. In addition, we generate a number of testable experimental predictions that can distinguish our theory from other accounts of OFC function. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Cereb Cortex Commun
                Cereb Cortex Commun
                cercorcomms
                Cerebral Cortex Communications
                Oxford University Press
                2632-7376
                2020
                26 November 2020
                26 November 2020
                : 1
                : 1
                : tgaa086
                Affiliations
                [1 ] Systems Neurobiology Research Unit, University of Stuttgart , Stuttgart D-70569, Germany
                [2 ] Department of Neurobiology, University of Stuttgart , Stuttgart D-70569, Germany
                Author notes
                Address correspondence to Dr Wolfgang Hauber, Systems Neurobiology Research Unit, University of Stuttgart, Pfaffenwaldring 57, Stuttgart D-70569, Germany. Email: hauber@ 123456bio.uni-stuttgart.de .
                Article
                tgaa086
                10.1093/texcom/tgaa086
                8152852
                34296142
                b09356e4-fdb7-4242-8f90-b70d03d39b03
                © The Author(s) 2020. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 September 2020
                : 6 November 2020
                : 6 November 2020
                Page count
                Pages: 9
                Funding
                Funded by: Deutsche Forschungsgemeinschaft, DOI 10.13039/501100001659;
                Award ID: HA2340/11-1
                Categories
                Original Article

                disconnection,effort,gaba,orbitofrontal cortex,ventral tegmental area

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